Article
Endocrinology & Metabolism
D. van Vliet, E. van der Goot, W. G. van Ginkel, H. J. R. van Faassen, P. de Blaauw, I. P. Kema, M. R. Heiner-Fokkema, E. A. van der Zee, F. J. van Spronsen
Summary: The study suggests that LNAA treatment in PKU patients does not require a phenylalanine-restricted diet. In PKU mice, LNAA treatment without phenylalanine restriction had comparable effects on brain monoamine concentrations compared to a strict phenylalanine-restricted diet.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Endocrinology & Metabolism
Allysa M. Dijkstra, Ninke van Vliet, Danique van Vliet, Cristina Romani, Stephan C. J. Huijbregts, Els van der Goot, Iris B. Hovens, Eddy A. van der Zee, Ido P. Kema, M. Rebecca Heiner-Fokkema, Francjan J. van Spronsen
Summary: Blood Phe remains the best predictor of brain biochemistry in PKU patients, but neurocognitive and behavioral outcomes cannot be fully explained by blood or brain Phe concentrations, necessitating the search for other additional parameters.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Cell Biology
Shira Ziegler, Jiyoung Kim, Jeffrey Ehmsen, Hilary Vernon
Summary: Amino acids are essential for protein synthesis and play key roles in various cellular functions. Genetic defects in amino acid metabolism can cause a group of rare but treatable diseases. This article discusses the pathophysiology, clinical features, and management of three disorders to showcase the diversity of amino acid metabolism disorders.
DISEASE MODELS & MECHANISMS
(2023)
Article
Neuroimaging
Stephanie Abgottspon, Raphaela Muri, Shawn E. Christ, Michel Hochuli, Piotr Radojewski, Roman Trepp, Regula Everts
Summary: In early-treated adults with PKU, cognitive performance and neural activation are slightly altered, with reduced neural activation in specific brain regions compared to healthy controls. These alterations are partly related to metabolic parameters, offering insights into the complex interplay between metabolic parameters, neural activation, and cognitive performance in individuals with PKU.
NEUROIMAGE-CLINICAL
(2022)
Review
Pediatrics
Mariangela Martino, Jacopo Sartorelli, Vincenza Gragnaniello, Alberto Burlina
Summary: Congenital hyperinsulinism is a group of diseases characterized by persistent hyperinsulinemic hypoglycemia, which can lead to neurological impairment. New technologies and discoveries in blood glucose monitoring and treatment have the potential to improve neurological outcomes.
FRONTIERS IN PEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Stephen J. J. Staklinski, Sarah Snanoudj, Anne-Marie Guerrot, Catherine Vanhulle, Francois Lecoquierre, Soumeya Bekri, Michael S. S. Kilberg
Summary: Asparagine Synthetase Deficiency (ASNSD) is caused by mutations in the ASNS gene and leads to microcephaly, seizures, brain atrophy, and developmental delays. A 9-year-old child with ASNSD was found to have compound heterozygous mutations and reduced proliferation in cells lacking asparagine. Enzymatic activity and protein expression studies in ASNS-null cells further elucidate the biological impact of ASNS mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maria Joao Pena, Raquel Costa, Ilda Rodrigues, Sandra Martins, Joao Tiago Guimaraes, Ana Faria, Conceicao Calhau, Julio Cesar Rocha, Nuno Borges
Summary: This study compared the metabolic effects of casein glycomacropeptide (GMP) and free amino acids (fAA) in rats, revealing differences in body weight, insulin levels, and GLP-1 production between GMP and fAA. The chronic consumption of different diets triggered varied metabolic responses, providing clues for further investigations into potential underlying mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Lennart Moritz, Katharina Klotz, Sarah Catharina Gruenert, Luciana Hannibal, Ute Spiekerkoetter
Summary: Phenylketonuria (PKU) is a common inborn error of metabolism caused by mutations in phenylalanine hydroxylase (PAH). PKU patients have elevated levels of phenylalanine and may experience intellectual disability. This study found distinct differences in metabolite profiles between PKU patients and healthy controls, as well as altered concentrations of metabolites in treated patients. The PKU submetabolome identified in this study reflects the effects of dietary adherence, compensatory metabolic pathways, and metabolic disturbances that cannot be corrected with diet. Potential therapeutic targets may be discovered to approximate the submetabolome of PKU patients to that of healthy controls and prevent long-term organ damage.
MOLECULAR GENETICS AND METABOLISM
(2023)
Review
Pediatrics
Alicia Turner, Kevin E. Glinton, V. Reid Sutton
Summary: This article presents new therapeutic modalities for inborn errors of metabolism that are currently in clinical trials or recently approved by the FDA, including nonhuman enzyme therapies, gene therapy, and chaperone therapies. These new therapies offer more options for treatment and have the potential to improve outcomes.
CURRENT OPINION IN PEDIATRICS
(2022)
Article
Nutrition & Dietetics
Meriah S. Schoen, Usha Ramakrishnan, Jessica A. Alvarez, Thomas R. Ziegler, Xiangqin Cui, Rani H. Singh
Summary: This study compared choline consumption among individuals with phenylketonuria (PKU) to a reference sample and identified factors that may affect choline needs. The findings suggest that only a small percentage of PKU patients achieve adequate choline intake, and treatment methods can impact choline levels. Without fortified medical foods, choline and other related nutrient intake may be reduced. Regular monitoring of choline intake and increased fortification of medical foods could benefit this population.
Article
Nutrition & Dietetics
Iris Scala, Daniela Concolino, Anna Nastasi, Giulia Esposito, Daniela Crisci, Simona Sestito, Stefania Ferraro, Lucia Albano, Margherita Ruoppolo, Giancarlo Parenti, Pietro Strisciuglio
Summary: The study demonstrates that the use of slow-release large neutral amino acids (srLNAAs) can effectively prevent an increase in Phe levels following a Phe dietary load, maintaining stable plasma Phe levels. This method can increase tyrosine levels and decrease the Phe/Tyrosine ratio during acute oral Phe loads, with no adverse events reported.
Article
Biochemical Research Methods
Ines M. S. Guerra, Luisa Diogo, Marisa Pinho, Tania Melo, Pedro Domingues, M. Rosario Domingues, Ana S. P. Moreira
Summary: Phenylketonuria (PKU) is a metabolic disorder caused by impaired function of phenylalanine hydroxylase. Treatment involves restricting phenylalanine intake through dietary modifications. Analysis showed significant differences in plasma phospholipid composition between PKU children and healthy children, with higher levels of phosphatidylcholines containing polyunsaturated fatty acids (PUFA) in PKU group.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Chemistry, Analytical
Andrea Idili, Julian Gerson, Tod Kippin, Kevin W. Plaxco
Summary: This study utilized real-time EAB sensors to monitor plasma phenylalanine levels in live animals, revealing previously unreported metabolic response phases. By analyzing hundreds of individual measurements, inter-subject variability, including significant differences related to feeding status, was identified. This approach has significant implications for understanding physiology and monitoring and treating metabolic disorders.
ANALYTICAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Arnaud Germain, Ludovic Giloteaux, Geoffrey E. Moore, Susan M. Levine, John K. Chia, Betsy A. Keller, Jared Stevens, Carl J. Franconi, Xiangling Mao, Dikoma C. Shungu, Andrew Grimson, Maureen R. Hanson
Summary: Post-exertional malaise (PEM) is a prominent symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). By monitoring plasma metabolites, this study found significant differences in metabolic response and recovery pattern between ME/CFS patients and healthy control participants after two maximal exercise tests. Glutamate metabolism was identified as a crucial factor in the metabolic disruptions that lead to PEM.
Article
Pharmacology & Pharmacy
Sara Parolisi, Chiara Montanari, Elisa Borghi, Chiara Cazzorla, Juri Zuvadelli, Martina Tosi, Rita Barone, Giulia Bensi, Cristina Bonfanti, Carlo Dionisi Vici, Giacomo Biasucci, Alberto Burlina, Maria T. Carbone, Elvira Verduci
Summary: Cognitive and psychiatric disorders are common in patients with inborn errors of metabolism (IEMs). Gut microbiota plays a role in behavior and cognition through the gut-brain axis. Recent research suggests that disrupted tryptophan metabolism, possibly caused by alterations in gut microbiota, may contribute to a broad spectrum of gut-brain axis disorders. Early-life diets also influence neurodevelopment and cognitive deficits in adulthood. Phenylketonuria (PKU) is an IEM that involves a restrictive diet, and significant changes in gut microbiota have been observed in PKU patients. The alteration of tryptophan metabolism, particularly the imbalance of the kynurenine pathway, has been associated with neurotoxic metabolites in PKU patients on amino acid medical foods supplementation.
PHARMACOLOGICAL RESEARCH
(2023)
Letter
Medical Laboratory Technology
Anneke C. Muller Kobold, Ido P. Kema, Janneke Dijck-Brouwer, Karin Koerts, Michiel Weening, Twan Storteboom, Jenny E. Kootstra-Ros, Martijn van Faassen, Ineke J. Riphagen
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2022)
Article
Endocrinology & Metabolism
D. van Vliet, E. van der Goot, W. G. van Ginkel, H. J. R. van Faassen, P. de Blaauw, I. P. Kema, M. R. Heiner-Fokkema, E. A. van der Zee, F. J. van Spronsen
Summary: The study suggests that LNAA treatment in PKU patients does not require a phenylalanine-restricted diet. In PKU mice, LNAA treatment without phenylalanine restriction had comparable effects on brain monoamine concentrations compared to a strict phenylalanine-restricted diet.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Endocrinology & Metabolism
Annet Vulto, Martijn van Faassen, Michiel N. Kerstens, Andre P. van Beek
Summary: This study compared cortisol pharmacokinetics and pharmacodynamics in patients on hydrocortisone substitution with or without adrenal crisis. The results showed differences in cortisol and cortisone excretion as well as in pharmacodynamics between patients with and without adrenal crisis, suggesting a biological predisposition in certain patients for the development of an adrenal crisis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Pharmacology & Pharmacy
Eric Rozenveld, Nieko Punt, Martijn van Faassen, Andre P. van Beek, Daan J. Touw
Summary: This study analyzed the pharmacokinetics of hydrocortisone in patients with adrenal insufficiency, incorporating protein binding states into the PK model. The new model showed improved predictive ability for free cortisol concentrations and better correlations between total and free hydrocortisone AUC(24) compared to the old model.
Article
Biochemical Research Methods
Bas Sleumer, Martijn van Faassen, Michel J. Vos, Rainer Bischoff, Ido P. Kema, Nico C. van de Merbel
Summary: The human growth hormone GH1 (22 kDa) is an important biomarker for growth disorders. A LC-MS/MS method was developed to accurately quantify GH1 and distinguish it from other isoforms. The method showed good performance in different sample types and storage conditions.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Zongye Cai, Siyu Tian, Theo Klein, Ly Tu, Laurie W. Geenen, Thomas Koudstaal, Annemien E. van den Bosch, Yolanda B. de Rijke, Irwin K. M. Reiss, Eric Boersma, Claude van der Ley, Martijn Van Faassen, Ido Kema, Dirk J. Duncker, Karin A. Boomars, Karin Tran-Lundmark, Christophe Guignabert, Daphne Merkus
Summary: Activation of the kynurenine pathway (KP) was observed in treatment-naive patients with pulmonary arterial hypertension (PAH). KP-metabolites were found to be associated with the response to PAH therapy and the long-term survival of PAH patients.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, General & Internal
Marwah Doestzada, Daria V. Zhernakova, Inge C. L. van den Munckhof, Daoming Wang, Alexander Kurilshikov, Lianmin Chen, Vincent W. Bloks, Martijn van Faassen, Joost H. W. Rutten, Leo A. B. Joosten, Mihai G. Netea, Cisca Wijmenga, Niels P. Riksen, Alexandra Zhernakova, Folkert Kuipers, Jingyuan Fu
Summary: This study systematically investigated the associations between branched-chain amino acids (BCAAs) and cardiometabolic diseases (CMD), and found significant correlations but no causal relationships between BCAAs and CMD parameters. Specific associations were identified for isoleucine, and the association of valine was influenced by obesity status. These findings highlight the clinical importance of individual BCAAs in the diagnosis, prevention, and treatment of CMD.
Article
Veterinary Sciences
Marit F. F. van den Berg, Hans S. S. Kooistra, Guy C. M. Grinwis, Sebastiaan A. A. van Nimwegen, Martijn van Faassen, Ido P. P. Kema, Erik Teske, Sara Galac
Summary: This study reported the reference intervals for free metanephrines in plasma, urine, and saliva, and determined the diagnostic performance of plasma free normetanephrine and metanephrine in dogs with pheochromocytoma, hypercortisolism, and nonadrenal illness. With the establishment of these reference intervals, biochemical testing for pheochromocytoma in dogs can be significantly improved, and measurement of plasma free normetanephrine is superior to free metanephrine in dogs with pheochromocytoma.
JOURNAL OF VETERINARY INTERNAL MEDICINE
(2023)
Article
Medical Laboratory Technology
Bas Sleumer, Jordan Zwerwer, Martijn van Faassen, Michel J. Vos, Rainer Bischoff, Ido P. Kema, Nico C. van de Merbel
Summary: A LC-MS/MS method was developed to quantify sex hormone binding globulin (SHBG) in serum and plasma without an immunocapture step. The method demonstrated good correlation with the Abbott Alinity immunoassay, and improved lab-to-lab consistency of results.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2023)
Article
Neurosciences
Anne B. Foreman, Jana V. van Vliet-Ostaptchouk, Martijn van Faassen, Ido P. Kema, Bruce H. R. Wolffenbuttel, Pieter J. J. Sauer, Arend F. Bos, Sietske A. Berghuis
Summary: This study aimed to determine the effects of exposure to substances that affect neurobehaviour on attention and concentration during adolescence. The results showed that girls had higher concentrations of parabens than boys, and methylparaben and ethylparaben concentrations were associated with attention and hyperactivity. However, propylparaben concentrations were associated with poorer attention. Bisphenol concentrations were not associated with attention and concentration.
Article
Multidisciplinary Sciences
Nantia Othonos, Riccardo Pofi, Anastasia Arvaniti, Sarah White, Ilaria Bonaventura, Nikolaos Nikolaou, Ahmad Moolla, Thomas Marjot, Roland H. Stimson, Andre P. van Beek, Martijn van Faassen, Andrea M. Isidori, Elizabeth Bateman, Ross Sadler, Fredrik Karpe, Paul M. Stewart, Craig Webster, Joanne Duffy, Richard Eastell, Fatma Gossiel, Thomas Cornfield, Leanne Hodson, K. Jane Escott, Andrew Whittaker, Ufuk Kirik, Ruth L. Coleman, Charles A. B. Scott, Joanne E. Milton, Olorunsola Agbaje, Rury R. Holman, Jeremy W. Tomlinson
Summary: The study suggests that inhibiting 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) with AZD4017 could mitigate the adverse effects of glucocorticoids while preserving their anti-inflammatory actions. Co-treatment of AZD4017 with prednisolone shows potential in limiting the adverse effects of glucocorticoids.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yuqi Wang, Bernd Riedstra, Bonnie de Vries, Martijn van Faassen, Alle Pranger, Ido Kema, Ton Groothuis
Summary: Mothers can influence offspring phenotypes by transferring non-genetic information to the young, providing them with a flexible tool to adjust their developmental trajectory in fluctuating environments. This study investigated the plasticity of embryonic metabolism of maternal androgens in Rock pigeons, finding that embryos have certain plasticity in response to maternal androgen levels depending on maternal signals.
SCIENTIFIC REPORTS
(2023)
Article
Neurosciences
Celien Tigchelaar, Willemien D. D. Muller, Sawal D. D. Atmosoerodjo, Klaas J. J. Wardenaar, Ido P. P. Kema, Anthony R. R. Absalom, Martijn van Faassen
Summary: A study on neurologically healthy patients undergoing spinal anesthesia found that there is a concentration gradient for most of the investigated biomarkers between the ventricles and the lumbar region. The results contribute to the understanding of neurobiology and emphasize the importance of standardized procedures for cerebrospinal fluid handling for comparison between studies.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Chemistry, Medicinal
Annelies Heylen, Yannick Vermeiren, Ido P. Kema, Martijn van Faassen, Claude van der Ley, Debby Van Dam, Peter P. De Deyn
Summary: Despite distinct clinical profiles, ALS and FTD patients share pathological features, with a substantial percentage of patients displaying a mixed disease phenotype. Kynurenine metabolism plays a role in dementia-associated neuroinflammation and has been linked to both diseases. Kynurenine pathway metabolite levels were significantly lower in ALS patients compared to FTD, EOAD, and control subjects in multiple brain regions. This suggests that the contribution of kynurenine metabolism in neuroinflammation is lower in ALS than in FTD or EOAD, possibly due to differences in age of onset.
Meeting Abstract
Obstetrics & Gynecology
Z. Wang, A. Van der Veen, H. Groen, A. E. P. Cantineau, A. Van Oers, J. M. Hawley, B. G. Keevil, H. J. R. Van Faassen, I. P. Kema, A. Hoek
HUMAN REPRODUCTION
(2022)
